Picornaviruses are among the largest of animal virus families that cause major diseases, such as poliomyelitis (poliovirus), hepatitis (hepatitis A virus), foot-and-mouth disease (FMDV), severe respiratory disease (coxsackievirus), inflammation of cardiac tissue (cardioviruses), and the common cold (human rhinovirus). Rhinoviruses, in particular, are the major causative agents of the common cold in humans. It has been estimated that the cost of this illness to the United States economy is $40 billion per year. Therefore, the prevention or cure of the common cold remains a goal of high impact.
For numerous reasons, at this time, there is no commercially-available vaccine for human rhinovirus infection. Among such reasons, it is well documented that rhinoviruses exhibit more than 100 serotypes. Each serotype is generally defined by the recognizable antigenic determinants (i.e., epitopes) which exist on the surface of the viruses. Accordingly, rhinoviruses may exhibit any of more than 100 immunologically distinct serotypes, which renders producing an effective vaccine against such viruses problematic. Indeed, using currently-available technology, patients must be injected with attenuated or inactive viruses representing each serotype or several peptides for each serotype to elicit sufficient protection against the common cold—making vaccination against rhinovirus unfeasible.
To further complicate matters, the available epitopes on such rhinoviruses are not linear; rather, the epitopes are three-dimensional. More particularly, it is believed that the major antigenic sites on the virus consist of several peptide loops. As a result, antibodies raised against such epitopes recognize a three-dimensional structure rather than a linear polypeptide or portion thereof.
Indeed, in the case of human rhinovirus 14, for example, antibodies raised against correspondingly linear peptides are usually non-reactive against the authentic virion. Therefore, for many viruses, such as rhinoviruses, attenuated or intact (dead) virions must be used for vaccination. Given that there are at least 100 serotypes of human rhinoviruses, such an approach is impractical (if not impossible).
The present invention circumvents many of the above problems and offers novel methods and compositions to generate and design effective peptide vaccines against highly variable viruses, including human rhinoviruses (and other picornaviruses).